DESCRIPTION: (Applicant's Description) Voltage-gated calcium channels couple electrical stimuli to important physiological events such as muscle contraction, transmitter secretion, and gene expression. Inherited calcium channelopathies have been identified in patients with spinocerebellar ataxia, hemiplegic migraine, and episodic ataxia type 2. In addition, calcium channels have been implicated in epilepsy and Lambert-Eaton myasthenic syndrome. Given the diverse role of calcium channels in physiological and pathophysiological conditions, insights into the coupling of electrical signals to cellular functions by the calcium channel would be beneficial. The broad perspective of this proposal is to further understand the coupling of excitation to the secretion of neurotransmitter at peripheral and central synapses. N-type and P/Q-type calcium channels are predominately involved in exocytosis at these synapses. Both channels selectively interact with members of the vesicle docking/fusion apparatus. These interactions are required for the coupling of excitation to secretion. However, the molecular basis for these protein-protein interactions remains unknown. Furthermore, the mechanism instituting the biphasic calcium dependence of these interactions has not been elucidated. This proposal aims to investigate the factors determining and regulating the interaction of presynaptic calcium channels with exocytotic proteins which will enhance the understanding of neurotransmitter release.